Imlunestrant/Abemaciclib/Selinexor in Ovarian and Endometrial

NCT07832227 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 26-444
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase 2, interventional treatment trial evaluating imlunestrant, abemaciclib, and selinexor in two separate patient cohorts: low grade serous ovarian cancer and endometrioid endometrial cancer. The study is non-randomized and open-label. Treatment is administered in the outpatient setting, with a 14-day Cycle 0 followed by 28-day treatment cycles.

Conditions

Endometrial Cancer; Low Grade Ovarian Serous Adenocarcinoma

Keywords

Low grade serous ovarian cancer; Endometrioid endometrial cancer; CDK4/6; XPO1; SERD; Abemaciclib; Imlunestrant; Selinexor; Ovarian cancer; Endometrial cancer; LGSOC; EEC

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

  Treatment duration depends on individual response, evidence of disease progression, and treatment tolerance. On average, up to 1 year.

Secondary Outcomes (6)

• Progression-Free Survival at 6 Months (PFS6)

  6 months

• Median Overall Survival (OS)

  Survival status is assessed every 6 months for up to 3 years following the end-of-treatment assessment, or until death, whichever occurs first. Treatment duration depends on individual response, disease progression, and treatment tolerance.

• Median Progression-Free Survival (PFS)

  Tumor assessments are performed every 8 weeks during treatment. Treatment duration depends on individual response, evidence of disease progression, and treatment tolerance. On average, up to 3 years.

• Treatment-Related Adverse Events (TRAE) Rate

  AE assessments are performed at all study visits during treatment, and adverse events are collected through 30 days after the end of treatment. Treatment duration depends on individual response. On average, up to 1 year.

• Change in Ki67 Expression Rate from Cycle 0 to Cycle 2

  The first biopsy is collected on Day 8 of Cycle 0, and the second biopsy is collected on Day 1 of Cycle 2. Cycle 0 is 14 days, and Cycles 1 and 2 are 28 days each.

Study Arms (2)

1A - Low grade serous ovarian cancer cohort

EXPERIMENTAL

Participants in Cohort 1A receive combination treatment with imlunestrant, abemaciclib, and selinexor. Treatment is outpatient, with a 14-day Cycle 0 followed by 28-day cycles.

Drug: Imlunestrant; Drug: Abemaciclib; Drug: Selinexor

1B - Endometrioid endometrial cancer cohort

EXPERIMENTAL

Participants in Cohort 1A receive combination treatment with imlunestrant, abemaciclib, and selinexor. Treatment is outpatient, with a 14-day Cycle 0 followed by 28-day cycles.

Drug: Imlunestrant; Drug: Abemaciclib; Drug: Selinexor

Interventions

Imlunestrant DRUG

Oral study drug Taken once per day

1A - Low grade serous ovarian cancer cohort; 1B - Endometrioid endometrial cancer cohort

Abemaciclib DRUG

Oral study drug Taken twice per day

1A - Low grade serous ovarian cancer cohort; 1B - Endometrioid endometrial cancer cohort

Selinexor DRUG

Oral study drug Taken once per week

1A - Low grade serous ovarian cancer cohort; 1B - Endometrioid endometrial cancer cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For Cohort 1A: Participants must have histologically confirmed diagnosis of low-grade serous carcinoma of ovary, fallopian tube or peritoneum that is recurrent or metastatic and/or resistant to standard therapies; original diagnosis of de novo low-grade serous carcinoma or original diagnosis of serous borderline tumor with subsequent diagnosis of low-grade serous carcinoma are allowed. Participants whose tumors contain both low-grade serous carcinoma and high-grade serous carcinoma are not eligible.
• For Cohort 1B: Participants must have cytologically or histologically confirmed endometrial cancer that is recurrent or metastatic and/or resistant to standard therapies. Participants must have histologically confirmed either i) endometrioid endometrial cancer or ii) endometrial carcinosarcoma with endometrioid epithelial component.
• For both cohorts, tumor must be TP53 wild-type as determined by immunohistochemistry (IHC) or via CLIA-certified targeted NGS.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.
• For Cohort 1A: After the safety lead-in, participants must have biopsiable disease in a lesion that is not being utilized as the target lesion for RECIST assessment and willing to undergo two on-treatment biopsies.
• (NOTE: If a patient is included in the safety lead-in, the presence of biopsiable disease and willingness to undergo serial on-treatment biopsies is not required. After the safety lead-in, this requirement will remain for 14 participants, after which the biopsy requirement will no longer be mandatory for enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Appendix A)
• Age ≥ 18 years
• Participants must have normal organ and bone marrow function within 14 days before starting protocol therapy as defined below:
• Hematologic
• ANC ≥1.5 × 10\^9/L
• Platelets ≥100 × 10\^9/L Patients must have at least a 1-week interval from the last platelet transfusion prior to the screening platelet assessment.
• Hemoglobin
• ≥9 g/dL Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
• Hepatic

You may not qualify if:

• Participants who have had chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of protocol therapy. Participants who have had hormonal therapy within 2 weeks of the first dose of protocol therapy. Participants who have received experimental treatment within the last 28 days or 5 half-lives, whichever is shorter, prior to initiation of study therapy
• Patients who had wide-field radiotherapy ≤4 weeks (defined as involving ≥25% of the bone marrow), or limited field radiation for palliation ≤1 week prior to initiation of study therapy.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy administration (e.g., have residual toxicities \> Grade 1) with the exception of alopecia. Patients with stable Grade 2 neuropathy that does not affect ability to perform ADLs or who have clinically recovered from prior adverse events but remain on appropriate medical management (e.g. therapeutic anticoagulation for thromboembolic events; antihypertensives for hypertension) may also be considered eligible for the study after discussion with the sponsor-investigator). Patients with residual Grade 2 anemia who meet the marrow function criteria as defined in 3.1.8 will also be considered eligible. Participants with prior Grade 2 endocrine toxicities (hypothyroidism, adrenal insufficiency, etc) from checkpoint inhibitor therapy that are well managed with hormone supplementation are allowed.
• Participants who are receiving any other investigational agents for this condition.
• Participants may not have had prior receipt of abemaciclib or any CDK4/6 inhibitor.
• Participants may not have had prior receipt of selinexor or any XPO1 inhibitor.
• Participants with an inability or unwillingness to take supportive medications such as anti-nausea and anti-anorexia agents as recommended by NCCN Clinical Practice Guidelines in Oncology (NCCN CPGO) for antiemesis and anorexia/cachexia.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to imlunestrant, abemaciclib and selinexor.
• Participants with active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment.
• Participants who at the time of study enrollment are known to require concomitant therapy with strong CYP3A4 inducers, or strong inhibitors of CYP3A4. Due to potential drug interactions, concomitant use of these medications is not permitted for the duration of treatment on trial. Participants are eligible for study entry if an appropriate substitution is made prior to the first dose of study medication.
• Pregnant women are excluded from this study because of the apoptotic and cytostatic effects of imlunestrant, abemaciclib and selinexor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued if the mother is treated with the study drugs.
• Any gastrointestinal dysfunctions that could interfere with the absorption of study drugs (e.g., bowel obstruction, inability to swallow tablets, malabsorption syndrome, unresolved nausea, vomiting, diarrhea).
• Major injuries or surgery within 28 days prior to starting study treatment and/or planned major surgery during the on-treatment study period.
• Hospitalization for any reason within 14 days of starting study treatment.
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease/pneumonitis, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Eli Lilly and Company: collaborator
• Karyopharm Therapeutics Inc: collaborator

MeSH Terms

Conditions

Endometrial Neoplasms; Ovarian Neoplasms

Interventions

Imlunestrant; abemaciclib; selinexor

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Panagiotis Konstantinopoulos, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Panagiotis Konstantinopoulos, MD, PhD

CONTACT

6176322334; Panagiotis_Konstantinopoulos@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 14, 2026
• First Posted: September 21, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): August 1, 2029
• Last Updated: September 21, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Contact the Belfer office for Dana -Farber Innovations (BODFI) at innovations@dfci.harvard.edu